Coeliac disease (CD) is a complex immunological response to the presence of wheat gluten in the gut. Generally the disease manifests through malabsorption of the upper small intestine caused by villus atrophy and crypt hyperplasia resulting from the inappropriate immune response to gluten in this region. Symptoms of the disease often reflect the malabsorption occurring in the gut, i.e. growth defects, anaemia and diarrhoea although asymptomatic patients are common. If left untreated the disease may lead to complications such as small intestinal lymphoma (Logan et al., 1989, Gastroenterology 97:265-271), and small bowel adenocarcinoma (Begos et al., 1995, J Clin Gastroenterol 20:233-6).
Until recently the recognised method of diagnosis for coeliac disease as defined by the European Society for Paeditric Gastroenterology and Nutrition (ESPGAN) was a source of considerable stress to patients due to repeated intestinal biopsy over long periods of time. Extensive research into the progression of the disease and into non-invasive tools for its diagnosis has led to the identification of several broadly defined serological markers. In the light of these discoveries EPSGAN have revised their criteria for CD diagnosis (Walker-Smith et al, 1990, Report of working group of European Society of Pediatric Gastroenterology and Nutrition) so that biopsy is limited to one sample, taken at presentation, along with the presence of recognised CD serological markers that diminish with gluten withdrawal from the diet. Thus the research emphasis has shifted in recent years to the search for a serological test that is as at least as good as gut biopsy for CD diagnosis.
To date, the humoral aspect of coeliac disease has been grouped according to the antigens with which reaction has been shown in in vitro assays. Thus both IgG and IgA class anti-gliadin antibodies (AGA), anti-reticulin antibodies (ARA), and anti-endomysial antibodies (EMA) have been defined and investigated. Many papers, reviews and trials have been published on the relative efficacy of using each of these markers in various assay formats and each approach has its champion. Doubts over the specificity of AGA have persisted as it has become apparent that limited immune responses to gliadin along with other recognised food antigens can occur in a variety of gut disorders (Maki et al, 1995, In Howdle P D (ed): Coeliac Disease, Baillières Clin Gastroenterol 9:231-249). Of the other two groups of antibody the EMA have risen to prominence with the discovery by Dieterich et al. (1997, Nature Med 3:797-801) that Type II transglutaminase could be precipitated from cell extracts using AGA depleted serum from patients with chronic CD. The human Type II TG based ELISAs that rapidly followed proved to be both highly specific and sensitive and were obviously widely welcomed as a replacement for the antiquated and difficult to interpret immunofluorescent test using monkey oesophagus or human placenta sections.
It was soon apparent however that the results of clinical use of type II TG based assays very often failed to match these high levels of reliability. This inconsistency in the results may reflect the fact that much of the original research has been performed using sera from chronic coeliac patients whereas the clinical use of the assay has seen a wider variety of patients that have presented the disease in differing degrees of severity.
In addition to the poor clinical results seen with type II TG based ELISAs it is now becoming clear that several other antigens are involved in the autoimmune aspect of coeliac disease (Clemente et al., 2000, Gut 47:520-526) and that the original inference of Dieterich that type II TG is the only significant antigen has become invalid.
Hence, there is a need to improved methods of diagnosing coeliac disease.